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Excision Repair Cross Complementation Group 1 Immunohistochemical Expression Predicts Objective Response and Cancer-Specific Survival in Patients Treated by Cisplatin-Based Induction Chemotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

Authors' Affiliations: ¹ Hôpital Jean Verdier (APHP), Bondy, France; ² Université Paris XIII/Nord; ³ Hôpital Tenon (APHP); ⁴ Université Pierre et Marie Curie, Paris, France; ⁵ Institut Gustave-Roussy, Villejuif, France; and ⁶ Université Paris XI, Orsay, France

Requests for reprints: Pierre Fouret, Unité de recherche translationelle Thorax Tête et Cou, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France. Phone: 33-1-42-11-65-10; Fax: 11-33-1-42-11-60-94; E-mail: fouret{at}igr.fr.

Purpose: To assess the correlation of excision repair cross complementation group 1 (ERCC1) immunohistochemical expression with objective tumor response and cancer-specific survival in patients with locally advanced head and neck squamous cell carcinoma treated with cisplatin-based induction chemotherapy.

Experimental Design: The initial cohort was composed of 107 patients who were treated from 1992 to 1996 by an induction chemotherapy regimen for locally advanced head and neck squamous cell carcinoma. p53 mutations had previously been studied. Pretherapeutic biopsy samples from 96 patients with a known tumor response were available. Two independent observers blinded to clinical annotations evaluated ERCC1 immunohistochemical expression.

Results: Of 96 patients, 68 (71%; 95% confidence interval, 61-79%) had tumors that expressed ERCC1 intensively and diffusely. Using the logistic regression method, the 28 (29%) patients with tumors expressing ERCC1 at lower levels had a 4-fold greater odds of benefiting from an objective response to chemotherapy (odds ratio, 4.3; 95% confidence interval, 1.4-13.4; P = 0.01) compared with the group of 68 patients with high ERCC1 expression. ERCC1 and p53 status, but not their interaction, were independent predictors of tumor response. In a Cox proportional hazard model adjusted on age, TNM stage, tumor differentiation, and tumor localization, ERCC1 low expression was associated with a lower risk of cancer death (risk ratio, 0.42; 95% confidence interval, 0.20-0.90; P = 0.04) whereas p53 status had no prognostic value.

Conclusion: Our results suggest that those patients characterized by low ERCC1 expression are more likely to benefit from cisplatin induction chemotherapy compared with patients with high ERCC1 expression.